"Hope" Drives Quality of Life in Patients With Brain Metastases, But, the "Hope Center" Remains Elusive: An Analysis of NRG-CC003

Int J Radiat Oncol Biol Phys. 2025 Nov 1;123(3):642-652. doi: 10.1016/j.ijrobp.2025.06.3884. Epub 2025 Jul 2.

Abstract

Purpose: NRG-CC003 randomized 393 patients with small cell lung cancer to prophylactic cranial irradiation (PCI) with or without hippocampal avoidance (HA). "Hopefulness" is a cognitive construct with 3 components: goals, pathways, and agency. Hope is measurable with validated instruments. Since hope is cognitive in nature, the existence of a "hope center" in the brain-most likely in the hippocampus-has been hypothesized. One exploratory objective of NRG-CC003 posited that if hope levels were better maintained in patients randomized to PCI + HA, then the hippocampus would be implicated in the mechanism of hopefulness.

Methods and materials: PCI consisted of 10 fractions of 2.5 Gy. The Adult Hope Scale (AHS) was administered at time-zero and at 6 months. Regarding patient-reported outcome measures, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 was administered at baseline and at 3, 6-, 12-, 18- and 24-month intervals. Comparisons of AHS scores by arm were made using Wilcoxon-Mann-Whitney tests, and correlation of AHS with EORTC QLQ-C30 by Pearson correlation coefficients.

Results: Approximately 95% completed the AHS at baseline and 67% filled out the questionnaire at 6 months paralleling the completion rates of the conventional tools for QOL and neurocognition. When comparing hope levels (change from baseline to 6 months) there was no significant difference (P > .05) between the 2 arms of the trial. There was a correlation for the components of hopefulness with QOL; specifically, between change in agency score and QLQ-C30 global health status (ρ = 0.27, P < .0001) as well as between change in pathways score and QLQ-C30 global health status (ρ = 0.16, P = .022).

Conclusions: It is feasible to study hopefulness in the context of prospective trials conducted within the National Clinical Trials Network. The hippocampus could not be implicated as a critical structure in a central pathway that coordinates hopefulness. For the first time, validated tools established a relationship between hope and quality of life among cancer patients.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms* / prevention & control
  • Brain Neoplasms* / psychology
  • Brain Neoplasms* / radiotherapy
  • Brain Neoplasms* / secondary
  • Cognition
  • Cranial Irradiation* / methods
  • Cranial Irradiation* / psychology
  • Female
  • Hippocampus* / physiology
  • Hippocampus* / radiation effects
  • Hope*
  • Humans
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / psychology
  • Male
  • Middle Aged
  • Patient Reported Outcome Measures
  • Quality of Life* / psychology
  • Small Cell Lung Carcinoma* / psychology
  • Small Cell Lung Carcinoma* / radiotherapy
  • Small Cell Lung Carcinoma* / secondary